A quantum chemical study on the mechanism of glycinamide ribonucleotide transformylase inhibitor: 10-Formyl-5,8,10-trideazafolic acid

Biophys Chem. 2005 Dec 1;118(2-3):78-83. doi: 10.1016/j.bpc.2005.07.001. Epub 2005 Sep 28.

Abstract

A density functional theory (DFT) study is presented on the reaction mechanism of glycinamide ribonucleotide (GAR) with 10-formyl-5,8,10-trideazafolic acid (10f-TDAF), which is an inhibitor designed for GAR transformylase (GAR Tfase). There are three different paths for this system and the results indicate that inhibitor 10f-TDAF can form a very stable intermediate with the substrate GAR or generate an imine bond with GAR by elimination of water. The results have verified the presumption from available experiments and implied that 10f-TDAF would be an important target for anti-neoplastic intervention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Chemical Phenomena
  • Chemistry, Physical
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Glutamates / chemistry*
  • Glutamates / pharmacology
  • Glycine / analogs & derivatives
  • Glycine / chemical synthesis
  • Glycine / chemistry
  • Models, Chemical*
  • Molecular Structure
  • Phosphoribosylglycinamide Formyltransferase / antagonists & inhibitors
  • Quantum Theory*
  • Quinazolines / chemistry*
  • Quinazolines / pharmacology
  • Ribonucleotides / chemical synthesis
  • Ribonucleotides / chemistry
  • Stereoisomerism

Substances

  • Enzyme Inhibitors
  • Glutamates
  • Quinazolines
  • Ribonucleotides
  • glycinamide ribonucleotide
  • 10-formyl-5,8-10-trideazafolic acid
  • Phosphoribosylglycinamide Formyltransferase
  • Glycine